Signal transduction via CD43 (leukosialin, sialophorin) and associated biological effects in human mast cell line (HMC-1).
CD43 has been shown to be involved in the regulation of cellular adhesion and activation of leukocytes, but its functional significance for mast cell biology has been poorly defined. We demonstrate here that mAb engagement of surface CD43 on human leukemic (HMC-1) mast cells initiates a signaling cascade which involves protein kinase C, while tyrosine kinases appear to play a minor role, as evidenced by effects of different kinase inhibitors on homotypic aggregation induced via CD43. Furthermore, administration of an activating anti-CD43 mAb is shown to induce and promote TNF-alpha- and to enhance IL-8-secretion from HMC-1 cells, but it does not initiate histamine, tryptase, or LTC4 release, suggesting that the intracellular pathways leading to aggregation and release of certain mast cell mediators are differentially regulated. Additionally, engagement of CD43 on HMC-1 cells leads to down-regulation of CD43 surface expression, implying that CD43 may be potentially involved in its own regulation.
Babina
M
M
Department of Dermatology, Virchow-Klinikum, Humboldt-Universität zu Berlin, Germany.
Weber
S
S
Mammeri
K
K
Henz
B M
BM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D051917:Leukosialin; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C